Remyelination and the gut−brain axis

Multiple sclerosis (MS) is a neuroinflammatory disease of the central nervous system (CNS) that affects over 2.5 million people worldwide. Most patients develop a relapsing−remitting disease in their second or third decade, although some have a progressive disease from onset. Many of those with relapsing−remitting disease eventually progress into a secondary progressive phase in which there is no improvement, and, like primary progressive MS, there is a gradual worsening of clinical disease (1). In early disease, an immune-mediated inflammatory attack in the CNS leads to myelin loss (demyelination) and the beginning of axon and neuronal loss (2⇓–4). Inflammatory T cells play a key role in driving the disease in association with an innate immune response, and the activation of resident microglia. As myelin breaks down, macrophages infiltrate from the periphery. There are now many disease-modifying therapies that target the inflammatory and immune response and benefit many MS patients by reducing the relapse rate and severity of disease (1). However, none of these therapies have been clearly shown to promote restoration of myelin on demyelinated axons (remyelination), either in relapsing−remitting or progressive disease. Indeed, the greatest challenge in MS research at present is how to prevent or stop progression associated with axon loss in progressive disease (5). The most discussed approach to this issue is to develop therapies that promote remyelination. Remyelination will not only restore conduction and subsequent neurologic function (6), but will also protect axons from degenerating (7⇓⇓–10). Thus, enhancing remyelination is currently a much sought-after therapeutic strategy. In PNAS, McMurran et al. (11) investigate the previously unstudied connection between the microbiome and the CNS innate immune response, and, in particular, whether manipulation of the microbiome can promote remyelination (Fig. 1). Fig. 1. Remyelination is not enhanced by microbiome manipulation. A schematic of … [↵][1]1To whom correspondence may be addressed. Email: ian.duncan{at}wisc.edu. [1]: #xref-corresp-1-1